Is CSF1R p.Ser414Phe (c.1241C>T) pathogenic?

CSF1R p.Ser414Phe (c.1241C>T) is classified Conflicting classifications of pathogenicity in CSF1R (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-07). AlphaMissense: likely benign (0.2157); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CSF1R p.Ser414Phe (c.1241C>T)?

CSF1R p.Ser414Phe (c.1241C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CSF1R p.Ser414Phe (c.1241C>T) in the general population?

CSF1R p.Ser414Phe (c.1241C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about CSF1R p.Ser414Phe (c.1241C>T)?

AlphaMissense predicts likely benign (score 0.2157) — an in-silico prediction, not a clinical call.

CSF1R p.Ser414Phe

c.1241C>T · rs149753251 · VCV2342191

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2157 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2157	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -9.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,910 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000805% 13/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,491
Admixed American	0.00333%	30,003
European (non-Finnish)	8.47e-05%	1,180,026

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CSF1R
Protein: p.Ser414Phe
Coding: c.1241C>T
MANE Select: NM_001288705
dbSNP: rs149753251
Type: single nucleotide variant
Location: chr5:150070260 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 414: a β-strand; the ig-like c2-type 5 domain

Full CSF1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSF1R p.Ala299Val Uncertain significance ★★ ⚠ same condition
CSF1R p.Ala770Thr Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg41Gln Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg549Cys Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg710Cys Uncertain significance ★★ ⚠ same condition
CSF1R p.Gln173Arg Uncertain significance ★★ ⚠ same condition
CSF1R p.Glu628Ala Uncertain significance ★★ ⚠ same condition
CSF1R p.Ile215Val Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/csf1r-p-ser414phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown